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TRAIL Dependent Fratricidal Killing of gp120 Primed Hepatocytes by HCV Core Expressing Hepatocytes

Rizza, SA; Challagundla, KB; Natesampillai, S; Bren, GD; Sykora, J; Walczak, H; Badley, AD; (2011) TRAIL Dependent Fratricidal Killing of gp120 Primed Hepatocytes by HCV Core Expressing Hepatocytes. PLoS ONE , 6 (11) , Article e27171. 10.1371/journal.pone.0027171. Green open access

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Abstract

The mechanism by which HIV and HCV cooperatively accelerate hepatocyte damage is not clearly understood; however, each virus affects the TRAIL: TRAIL- receptor system. We, therefore, questioned whether the independent effects of HCV and HIV combine to synergistically result in TRAIL dependent hepatocyte killing. We describe that Huh7 hepatocytes treated with HIV gp120 results in both increase TRAIL-R2 expression and an acquired sensitivity to TRAIL mediated killing. Moreover HCV infection and HCV core expression alone in Huh7 cells upregulates TRAIL. Co-incubation of HIV gp120 primed hepatocytes with HCV core expressing hepatocytes results in the selective death of the HIV gp120 primed hepatocytes that is selectively blocked by TRAIL–R2-Fc fusion protein. Liver biopsies from HIV mono-infected patients have increased TRAIL-R2; biopsies from HCV infected patients have increased TRAIL, while co-infected liver biopsies have increased PARP cleavage within hepatocytes indicating enhanced apoptosis. These findings suggest a pathogenic model to understand why HIV/HCV co-infection accelerates liver injury.

Type: Article
Title: TRAIL Dependent Fratricidal Killing of gp120 Primed Hepatocytes by HCV Core Expressing Hepatocytes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0027171
Publisher version: http://dx.doi.org/10.1371/journal.pone.0027171
Language: English
Additional information: © 2011 Rizza et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1396521
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